Thermoplastic polyhydroxyurethanes (PHUs) were synthesized from cyclic carbonate aminolysis. Because of the hydroxyl groups in PHU, the choice of soft segment has a dramatic influence on nanophase separation in polyether-based PHUs. Use of a polyethylene glycol-based soft segment, which results in nanophase-separated thermoplastic polyurethane elastomers (TPUs), leads to single-phase PHUs that flow under the force of gravity. This PHU behavior is due to major phase mixing caused by hydrogen bonding of hard-segment hydroxyl groups to the soft-segment ether oxygen atoms. This hydrogen bonding can be suppressed by using polypropylene glycol-based or polytetramethylene oxide (PTMO)-based soft segments, which reduce hydrogen bonding by steric hindrance and dilution of oxygen atom content and result in nanophase-separated PHUs with robust, tunable mechanical properties. The PTMO-based PHUs exhibit reversible elastomeric response with hysteresis, like that of conventional TPUs. Because of nanophase separation with broad interphase regions possessing a wide range of local composition, the PTMO-based PHUs also demonstrate potential as novel broad-temperature-range acoustic and vibration damping materials, a function not observed with TPUs.